1. Field of the Invention
The present invention relates to a liquid drug composition, and more particularly to a substantially taste masked aqueous liquid pharmaceutical composition that contains an otherwise unpleasant tasting drug.
2. Description of Related Art
The most convenient and commonly employed route of drug delivery has been by oral ingestion, either in liquid or solid formats. The unpalatable taste of most drugs is generally not a problem with solid dosage formats, which are intended to be swallowed whole. In the case of capsules, the hard gelatin shell prevents the drug from being tasted during the short transit time in the mouth. Tablets, on the other hand, can be coated with sugar or film forming polymers for tastemasking.
Many children and some adults however have difficulty swallowing solid dosage formats, and in this case, the drug is given in liquid form, either as syrup or suspension. Most drugs however are bitter, and this can lead to poor patient compliance. Because the threshold for bitterness is low, only a very small amount of dissolved drug is needed for perception of bitterness.
The prior art has shown extensive use of one or a combination of different flavoring methodologies to mask the bitter taste of drugs. For example, a flavor can be selected that complements the taste of the preparation, or a flavor with a longer intensity and stronger taste than the drug can be used. High levels of sweetening agents are often used to overwhelm bitterness with sweetness. The taste buds may also be anesthetized by menthol or mint flavors. These approaches are generally not very effective in masking the taste of a bitter drug, and a flavoring system that works with one drug usually does not apply to another drug.
The prior art also indicates that taste masking could also be achieved by increasing the viscosity of liquid preparations. Various combinations of viscosity modifiers for taste masking exist in the patent literature. For example, U.S. Pat. No. 5,616,621 provides taste masked liquid preparations by increasing the viscosity with a combination of polyethylene glycol and sodium carboxymethylcellulose; U.S. Pat. No. 5,658,919 discloses taste masking of acetaminophen suspension using a suspending system consisting of xanthan gum and a mixture of cellulosic polymers. The increase in viscosity is assumed to limit the contact of the drug with the tongue, presumably by slowing down salivary water uptake into the viscous liquid medicament, which can lead to dilution and dissolution of the ingested medication. This approach is only moderately successful in reducing bitterness especially at high drug loading. While bitterness may be reduced at the onset, bitter aftertaste becomes prominent after swallowing because thick preparations are more difficult to wash down thus leaving behind some residual viscous liquid medicament in the mouth after swallowing. This bitter aftertaste is more prominent with water intake due to the reduction in viscosity and dilution of the residual liquid medicament and subsequent dissolution of the drug in the mouth.
Several other approaches have been pursued to address the unpleasant taste of a drug in a liquid format. U.S. Pat. No. 5,730,997 illustrates the use of a hyperosmotic liquid using a sugar derivative and maltose syrup for taste masking. U.S. Pat. No. 5,154,926 claims reduction of the bitter taste of acetaminophen syrup by using a water-soluble macromolecule with a polyhydric alcohol and/or polymer of a polyhydric alcohol of MW 300–400. U.S. Pat. Nos. 5,763,449 and 5,962,461 teach the use of a combination of povidone, C3–C6 polyol and ammonium glycyrrhizinate for taste masking. EP application 1025858 A1 discloses relief of bitterness of basic drugs by combining propylene glycol with povidone and/or copolyvidone.
The disclosure that follows illustrates another, more general solution to the problem of bad taste in liquid compositions containing either dissolved or dispersed drugs.